200909810 九、發明說明： 【發明所屬之技術領域】 曰本發明係關於奈米科技和奈米顆粒技術領域，特 別疋，於種使用DNA為媒介之靜電捕捉技術以組裝 具有單顆粒解析度之奈米顆粒式樣的方法及其應用。 【先前技術】 合成奈米顆粒之相關技術已為普遍所知。此外， 奈米顆粒的物理性質已被普遍研究出來。而此兩個因素 已使奈米顆粒被認為是奈米元件之關鍵構成元件之一。200909810 IX. Description of the invention: [Technical field to which the invention pertains] The present invention relates to the field of nanotechnology and nanoparticle technology, and particularly to the use of DNA-mediated electrostatic capture technology to assemble a single particle resolution The method of rice grain pattern and its application. [Prior Art] Related art for synthesizing nanoparticle is well known. In addition, the physical properties of nanoparticle have been generally studied. These two factors have made nanoparticles one of the key components of nanocomponents.
Wu 等人在 Applied Physics Letters, Vol. 81, pg. 4595 (2002)文中’已描述了控制電子行為的奈米 顆粒元件。Weiss 等人在 Applied Physics Letters, Vol. 88，pg. 143507(2006)文中，以及 Andres 等人在 Sience, Vol. 272，pg. 1323(1996)文中，描述了類似 的奈米顆粒電子元件。Krenn等人在Physical Review Letters, Vol. 82, pg. 2590 (1999)文中，Lu 等人在 Advance Materials，Vol· 13，pg. 34 (2001)文中， 描述有關的奈米顆粒光電元件。此類奈米顆粒元件已引 起相當大的注意。此外，將奈米顆粒排列在預先選定的 特定位置上的技術’已開始在奈米元件和電路的整合上 扮演一個重要的角色。 可用來達成此類整合的傳統技術主要分成兩種， 即原子力顯微鏡（A F Μ )奈米顆粒的尖端操控和利用顆粒 6 200909810 間或顆粒/基材間的交互作用力形成的自組裝方法’。 自組裝令人特別感興趣，因為它具有優良的功能性和較 快的製造速度。各種各樣的相互作用機制已用於顆粒的 組裝或結合。然而，靜電的交互作用是顆粒自組裝的較 佳方法之一，可用於很多種類的材料之間，並且比其它 的特定結合方法更通用和更可靠。 近來已有研究團體使用靜電之交互作用機制來自 組裝顆粒，且因此提出證據以支持此種似乎大有可為的 方法。Fudouzi 等人在 Nanoparticle Research, Vol. 3, pg. 193 (2001)文中探討，使用電子束以產生靜電荷， 形成介電泳力誘導顆粒的自組裝。Jacobs等人在Nanoparticle elements that control electronic behavior have been described by Wu et al. in Applied Physics Letters, Vol. 81, pg. 4595 (2002). Similar nanoparticle electronic components are described by Weiss et al., Applied Physics Letters, Vol. 88, pg. 143507 (2006), and by Andres et al., Sience, Vol. 272, pg. 1323 (1996). Krenn et al., Physical Review Letters, Vol. 82, pg. 2590 (1999), Lu et al., Advance Materials, Vol. 13, pg. 34 (2001), describe related nanoparticle optoelectronic components. Such nanoparticle components have attracted considerable attention. In addition, the technology of arranging nanoparticles at pre-selected specific locations has begun to play an important role in the integration of nano-elements and circuits. The conventional techniques that can be used to achieve such integration are largely divided into two types, namely, the tip manipulation of atomic force microscopy (A F Μ ) nanoparticles and the self-assembly method using the interaction between particles 6 200909810 or particles/substrates. Self-assembly is of particular interest because of its excellent functionality and fast manufacturing speed. A variety of interaction mechanisms have been used for the assembly or binding of particles. However, electrostatic interaction is one of the better methods of self-assembly of particles, can be used between many types of materials, and is more versatile and reliable than other specific bonding methods. Recently, research groups have used electrostatic interaction mechanisms to assemble particles, and therefore present evidence to support such seemingly promising methods. Fudouzi et al., Nanoparticle Research, Vol. 3, pg. 193 (2001), explore the use of electron beams to generate electrostatic charges that form dielectrophoretic forces to induce self-assembly of particles. Jacobs et al.
Advance Materials，Vol. 14，pg. 1553 (2002)文中 描述一種奈米靜電複印技術的發展，其中是將奈米顆粒 組裝到經由奈米接觸而注入電荷所產生的電荷式樣 上。Tzeng 等人在 Advance Materials，Vol. 18，pg 1147 (2006)文中，探討使用靜電力顯微術，是一種來 建立高解析度的靜電式樣，然後能吸引溶液内的顆粒。 這些傳統方法所能達到之顆粒的線寬解析度是在3〇至 奈米的範圍内，且受到顆粒線橫戴面内所存在 多個顆粒的限制。然而，這些已知的方法均無法 百 有單顆粒線寬的解析度。 一、 已知將靜電捕捉方法與選擇性分子結合方法综人 起來應用，便能形成複雜的奈米顆粒超級結構。一 用的例子就是分子電子元件，由於此元件具有高度空g 7 200909810 使用率、低功率消耗、和低製造成本有關的優勢，在現 代的半導體元件中有極佳的評價。經由選擇性結合所 做成的分子電子元件有許多例子存在。Mirkin等人在 Nature, Vol. 382，607-609 (1996)文中即描述 了一種 以經常被使用的硫醇金膠狀顆粒複合物透過以選擇性 結合方法而製作成的分子電子元件，這是最常被使用的 方式。其他也有以DNA作為模板以組裝材料。參見 Braun et al. Nature, Vol. 391， pg. 775 (1998)文 獻；Keren et al. Science Vol. 302，pg. 1380 (2003) 文獻；Nakao，etal. Nano Letters. Vol. 3，pg. 1391 (2003); Linetal. Advanced Materials, Vol. 18, pg. 1517 (2004)文獻；和 Warner etal. Nature Materials, Vol. 2，pg· 272 (2003)等文獻資料均以具有極佳優勢 的DNA分子進行自組裝，因為具有精密的組成成分以 及精確的雜合配對特性。（參見Seeman，Nature, Vol. 421，pg· 427 (2003))。然而，使用上述的大部份方法 仍然無法在一個特定的位置上達到單顆粒解析度的式 樣。 【發明内容】 本發明為一種利用DNA為媒介之靜電捕捉技術以 組裝具有單顆粒解析度之奈米顆粒式樣的方法及其應 用。根據本發明，以生物素修飾之DNA分子的庫倫吸 引，和奈米顆粒的附著以產生金奈米顆粒鏈。根據本發 200909810 明的方法，以一個集中及精確定位的電子束在可控制的 劑量程度下產生基本的電荷式樣。準此’以此鏈可作 為連接導線或單電子電晶體。 根據本發明的方法，利用靜電捕捉生物素修飾之 DNA分子進而吸附硫醇金顆粒，在預先設計的位置上產 生具有單顆粒解析度之奈米顆粒式樣。在較佳實施例 上，使用之金（Au)顆粒的直徑約為13奈米。利用電子 束寫入，在矽基材上產生靜電荷式樣以固定極少數的募 核甘酸分子，進而吸附個別的金顆粒，因此可形成單 線式樣。 本案發明者已經確定在本發明的方法中，寡核甘 ，的導人是獲得本㈣有利結果的-侧鍵目素。沒有 寡核甘酸’使用已知傳統上靜電捕捉方法並無法獲得單 顆粒的解析度。 、本發明採行的方法是可以製作一維的顆粒列陣， 並於顆粒之岐立高與低線性f子穿遂連結，可分別成 為具功能性的連接導線和單電子元件^此外，本方法可 2特^ $求位置上製造其他功能性元件，如奈米級的 '皮導陣列、感測器和光電元件。 因此本發明的方法可提供—種使用最少微影製程 ^方法’以製造個別的奈米元件和建造奈米尺度的 絲二系、、’充提仏種在指定之奈米位置上建造單線顆粒 内、方法。的正電荷被產生於—個奈米尺度的區域 ’以庫倫力來吸引—小叢的生物素修飾之DM分子。 200909810 然後，生物素修飾之DMA分子與金顆粒結合以形成所 要的顆粒式樣。對於電子元件上的應用，本發明的方法 可使金顆粒形成可導電的奈米導線。在奈米電子元件和 奈米組合系統内所使用之連接導線和單電子電晶體的 發展，則是本發明方法的應用範例。 下述的詳細說明和附圖將使本發明的其它目的和 特徵更為明顯。然而，必須了解的是，圖的設計只為了 圖示目的，而非本發明之限制，因此需參考所附的申請 專利範圍。需更進一步了解，圖示並不一定是按比例描 繪，且除非另有說明，否則圖示僅說明此處所述之架構 和程序的觀念。 【實施方式】 本發明為一種利用DNA為媒介之靜電捕捉技術以 組裝具有單顆粒解析度之奈米顆粒式樣的方法，及其應 用。根據本發明，以生物素修飾之DNA分子的庫倫吸 引和奈米顆粒的附著以產生金奈米顆粒鏈。根據本發明 的方法，以一個集中和精確定位的電子束在可控制的劑 量程度下產生基本的電荷式樣。準此，以此鏈作為連接 導線或單電子電晶體。 根據本發明的方法，利用靜電捕捉生物素修飾之 MA分子進而吸附硫醇金顆粒，在預先設計的位置上產 生具有單顆粒解析度之奈米顆粒式樣。在較佳實施例 中，使用之金（Au)顆粒的直徑約為13奈米。利用電子 200909810 束寫入，在石夕基材上產生靜電荷式樣以固定極少數的寡 核甘酸分子，進而吸附個別的金顆粒上，因此形成單 線的式樣。 本發明者已經確定在本發明的方法中，寡核甘酸 的導入是獲得本發明之有利結果的一個關鍵因素。沒有 寡核甘酸，使用傳統已知之靜電捕捉的方法是無法獲得 單顆粒的解析度。 本發明預計採行的方法可以製作一維的顆粒列 陣，並於顆粒之間建立高與低線性電子穿遂連結，可分 別成為具功能性的連接導線和單電子元件。此外，本方 法可以在特定需求位置上製造其他功能性元件，如奈米 級的波導陣列、感測器和光電元件。因此本發明的方法 可提供一種使用最少微影製程步驟的方法，以製造個別 的奈米元件和建造奈米尺度的組合系統。 通常使用一個由電子搶產生和由電腦控制之數位 /類比轉換器（DAC)導引的聚焦電子束，在其光阻上產生 極細的式樣。此種電子束微影製程技術是半導體製造工 業内少數無遮罩微影製程系統之一。與光阻方式的曝光 不同，本發明的方法利用一個聚焦和有方向性的電子束 在以二氧化矽被覆的矽晶片上產生束缚電荷。當以電子 束照射一個絕緣基材時，將產生可作為電荷載子的電 子、電洞對。於此，電荷載子的一部份會被雜質、缺陷 或裂縫中和掉或束缚住，且在此時，其它載子可能逃離 基材的表面。如此產生的靜電不平衡，會使絕緣體帶有 11 200909810 負電或正電。 已知DNA分子在一般的緩衝溶液内稍微帶有負電 荷。如 Renoud 等人在 Phys, StatusSolidi. 2004，201， 2119文中内所述，被電子束照射的絕緣體經常帶有負 電。因此，少有以此方式來吸附固定DNA分子。然而， 如 Cazaux 在 J. Appl. Phy. Vol. 95， pg. 731 (2004) 文中内所述，在電子束照射到一個絕緣體的表面上時， 雖然照射區内的淨電荷是負的，在被照射的位置上會產 生一層具高度侷域性的正電荷，且其厚度約為電子的平 均逃離深度（5~20nm)。如Chi等人在Nanotechnology, Vol. 17，pg. 4854 (2006)文中内所述，只要在溫度 不高，亦無高電場的環境下’此局部電荷是十分穩定且 不隨時間衰減的。Advance Materials, Vol. 14, pg. 1553 (2002) describes the development of a nano-electrostatic copying technique in which nanoparticles are assembled into a charge pattern generated by injecting a charge via a nanocontact. Tzeng et al., Advance Materials, Vol. 18, pg 1147 (2006), explore the use of electrostatic force microscopy to create high-resolution electrostatic patterns that can then attract particles in solution. The linewidth resolution of the particles that can be achieved by these conventional methods is in the range of 3 Å to nanometers and is limited by the presence of multiple particles in the cross-section of the particle line. However, none of these known methods have the resolution of a single particle line width. First, it is known that the electrostatic trapping method and the selective molecular binding method can be combined to form a complex nanoparticle super structure. An example of use is molecular electronic components, which are highly evaluated in modern semiconductor components due to their high efficiency in terms of utilization, low power consumption, and low manufacturing cost. There are many examples of molecular electronic components made by selective bonding. Mirkin et al., Nature, Vol. 382, 607-609 (1996), describe a molecular electronic component produced by a selective bonding method using a thiol gold colloidal particle composite that is often used. The most commonly used way. Others also use DNA as a template to assemble materials. See Braun et al. Nature, Vol. 391, pg. 775 (1998); Keren et al. Science Vol. 302, pg. 1380 (2003); Nakao, et al. Nano Letters. Vol. 3, pg. (2003); Linetal. Advanced Materials, Vol. 18, pg. 1517 (2004); and Warner et al. Nature Materials, Vol. 2, pg. 272 (2003) and other literatures with DNA molecules with excellent advantages Self-assembly due to its precise composition and precise hybrid matching characteristics. (See Seeman, Nature, Vol. 421, pg. 427 (2003)). However, the use of most of the above methods still does not achieve a single particle resolution at a particular location. SUMMARY OF THE INVENTION The present invention is a method for assembling a nanoparticle pattern having a single particle resolution using a DNA-mediated electrostatic capture technique and an application thereof. According to the present invention, coulombic adsorption of a biotin-modified DNA molecule, and attachment of nanoparticles to produce a gold nanoparticle chain. According to the method of the present invention, the basic charge pattern is produced at a controlled dose level by a concentrated and precisely positioned electron beam. This chain can be used as a connecting wire or a single electron transistor. According to the method of the present invention, biotin-modified DNA molecules are electrostatically captured to adsorb thiol gold particles, and a nanoparticle pattern having a single particle resolution is produced at a pre-designed position. In a preferred embodiment, the gold (Au) particles used have a diameter of about 13 nm. Electron beam writing is used to create an electrostatic charge pattern on the tantalum substrate to immobilize a very small number of nucleotide molecules, thereby adsorbing individual gold particles, thereby forming a single line pattern. The inventors of the present invention have determined that in the method of the present invention, the leader of the oligonucleoside is the side-chain element which obtains the advantageous result of the present (IV). There is no oligonucleotide' and the resolution of single particles cannot be obtained using known conventional electrostatic capture methods. The method adopted by the invention can produce a one-dimensional array of particles, and is connected to the vertical and low linear f-substrate of the particles, and can be respectively a functional connecting wire and a single electronic component. The method can be used to create other functional components, such as nano-scale skin guide arrays, sensors, and optoelectronic components. Thus, the method of the present invention can provide a single-line particle at a specified nanometer position by using a minimum lithography process to fabricate individual nano-components and construct nanoscale silk secondary systems. Inside, method. The positive charge is generated in a region of the nanometer scale 'attraction by Coulomb force' - a small cluster of biotin-modified DM molecules. 200909810 The biotin-modified DMA molecule is then combined with the gold particles to form the desired particle pattern. For applications on electronic components, the method of the present invention allows gold particles to form electrically conductive nanowires. The development of connecting wires and single-electron transistors used in nanoelectronic components and nanocombining systems is an application example of the method of the present invention. Other objects and features of the present invention will become more apparent from the detailed description and appended claims. However, it must be understood that the design of the drawings is for illustrative purposes only and is not a limitation of the invention, so reference is made to the appended claims. The illustrations are not necessarily to scale, and the illustrations are merely illustrative of the concepts of the structures and procedures described herein. [Embodiment] The present invention is a method of assembling a nanoparticle pattern having a single particle resolution using a DNA-mediated electrostatic trapping technique, and an application thereof. According to the present invention, coulombic adsorption of biotin-modified DNA molecules and attachment of nanoparticles to produce a gold nanoparticle chain. In accordance with the method of the present invention, a substantially charged pattern is produced at a controlled dosage level with a concentrated and precisely positioned electron beam. As such, the chain is used as a connecting wire or a single electron transistor. According to the method of the present invention, the biomolecule-modified MA molecules are electrostatically captured to adsorb the thiol gold particles, and a nanoparticle pattern having a single particle resolution is produced at a pre-designed position. In a preferred embodiment, the gold (Au) particles used have a diameter of about 13 nm. Using electron 200909810 beam writing, an electrostatic charge pattern is generated on the Shixi substrate to fix a very small number of oligonucleotide molecules, thereby adsorbing individual gold particles, thus forming a single line pattern. The inventors have determined that the introduction of oligonucleotides in the method of the invention is a key factor in obtaining the advantageous results of the present invention. Without oligonucleotides, the resolution of single particles cannot be obtained using conventionally known methods of electrostatic capture. The present invention contemplates a method of fabricating a one-dimensional array of particles and establishing high and low linear electron-penetrating bonds between the particles, which can be functionally connected wires and single electronic components, respectively. In addition, the method can be used to fabricate other functional components such as nano-scale waveguide arrays, sensors, and optoelectronic components at specific demand locations. Thus, the method of the present invention provides a method of using a minimum of lithography process steps to fabricate individual nanocomponents and to construct a nanoscale composite system. A focused electron beam guided by an electronic grabber and a computer controlled digital/analog converter (DAC) is typically used to produce a very fine pattern on its photoresist. Such electron beam lithography process technology is one of the few maskless lithography process systems in the semiconductor manufacturing industry. Unlike the resistive exposure, the method of the present invention utilizes a focused and directional electron beam to create a bound charge on a tantalum wafer coated with ruthenium dioxide. When an insulating substrate is irradiated with an electron beam, an electron or hole pair that can serve as a charge carrier is generated. Here, part of the charge carriers may be neutralized or bound by impurities, defects or cracks, and at this time, other carriers may escape the surface of the substrate. The resulting electrostatic imbalance causes the insulator to be negatively or positively charged with 2009 20091010. DNA molecules are known to have a slight negative charge in a typical buffer solution. As described by Renoud et al. in Phys, Status Solidi. 2004, 201, 2119, insulators that are illuminated by electron beams are often negatively charged. Therefore, there are few ways to adsorb and immobilize DNA molecules in this way. However, as described in Cazaux, J. Appl. Phy. Vol. 95, pg. 731 (2004), when the electron beam is irradiated onto the surface of an insulator, although the net charge in the irradiation zone is negative, A highly localized positive charge is generated at the illuminated location, and its thickness is approximately the average escape depth of the electron (5-20 nm). As described in Chi et al., Nanotechnology, Vol. 17, pg. 4854 (2006), this local charge is very stable and does not decay with time as long as the temperature is not high and there is no high electric field.
Chi等人更進一步描述在靠近照射區的負電顆粒 可能克服遮蔽電位並附著在絕緣體的表面上。然而，如 欲以此方法直接吸附奈米金顆粒，由於所產生之二次電 子的雜亂散射，在此種情況下的靜電荷線通常會變寬， 因此，會產生多個顆粒線的寬度。減少電子束之劑量雖 可藉著減少吸引力以降低金顆粒的吸附數目，但經常會 降到吸附金顆粒的臨界值之下，無法真正達到僅僅吸附 單一顆粒之目的。 於此，先以低劑量之高度聚焦的電子束所產生的 靜電荷來吸引少量的生物素修飾之DNA分子。然後再 利用生物素内的硫來吸附溶液中之金顆粒。根據本發明 12 200909810 的方法，可以使用寡核甘酸分子來解決金顆粒與基材之 間吸引力的問題，因為它們與金顆粒比起來，較小也較 輕。第1(a)至1(g)圖所示為以此方法製造金奈米顆粒 單線式樣的掃描式電子顯微鏡（SEM)影像的圖示。在此 處，第1(b)、1(d)和1(g)圖内直的單線顆粒鏈之長度 的變化由數十奈米至數十微米。在特別的第1(a)圖内， 顯示4套經由不同電子束劑量所產生之” DM”字母的 金顆粒式樣。這些式樣建議了電子束的適當線劑量是在 2. 5到4. 0 nC/cm之間。在此例中，進一步增加劑量會 造成更多的顆粒被吸引在一起，使單線寬變粗，並因而 造成單線寬大於顆粒的尺寸。 第1(g)圖顯示一條單線金顆粒鏈的放大影像，其 中兩個臨近顆粒之間的平均距離約等於顆粒的尺寸。於 此，以電子束在各種脈衝間隔下做測試並沒有導致顆粒 間隔有相對應的變化。因此，顆粒的間隔主要由於金顆 粒之間微弱的排斥力，而不是來自靜電荷的距離分佈， 且本發明者已經確定此種結論是合理的。 從右上方到左下方，第1(a)圖内產生的4套” DNA”字母是在線分別暴露於1. 0、1. 5、2. 5、和4. 0 nC/cm電子束線劑量下。第1(b)至1(g)圖内，使用2. 5 nC/cm的單線暴露劑量來產生式樣。然而，對於所有式 樣而言，電子束脈衝之間，中心至中心的距離被設定為 一個特定的值。在較佳實施例内，特定的值是13. 6 nm。 第2圖所示為製造此種導電之奈米導線的一個完 13 200909810 整橋接循環步驟的圖示。如第2圖所示，在第2圖内重 複橋接循環的應用，以填補顆粒間之較大空隙以形成具 有顆粒間穿隧連結的金奈米顆粒導線（亦參見第3(b)至 3(g)圖）。 第3(a)至3(g)圖所示為製造之一維金顆粒陣列 和奈米導線的掃描式電子顯微鏡影像的圖示，其中第 3(a)圖顯示在實施橋接循環之前，單線的結構，第3(b) 和3(c)圖顯示在一次橋接循環之後，單線的結構，且 第3(d)至3(f)圖顯示在二次橋接循環之後，單線的結 構。第3(g)圖所示為固定於電極之間的金顆粒奈米導 線以產生可進行電性測量的性能，且如第3(g)圖所示， 為了創造出電子組件，金顆粒需密切連接以容許電子的 傳導。本發明者亦已經確定施加的循環愈多，導線的電 阻將變得越低，其中導線在室溫下具有線性的電流-電 壓（I-Vb)特性，且其電阻值大約分佈成兩群。 第4圖所不為樣品數與其母10 0 ηιπ在室溫下電阻 函數的長條分佈圖的圖示。即第4圖所示為二次橋接循 環組裝之導線所測得之電阻的長條分佈圖。參考第4 圖，清楚地顯示導線有低的電阻（高的穿透率）或極高的 電阻（低的穿透率）。此種分歧的行為可歸因於兩種橋接 機制，即（1)若顆粒僅由生物素連結，則距離很小且導 線電阻很低，以及（2)若顆粒由20-鹼基聚-A核甘酸 (5’ -(A)20-3’ ）或（20A)和 7-鹼基聚-T 核甘酸（5’ -(T)7-3’）或（7T)的混成來連結，則顆粒的距離變得較 200909810 大，且導線電阻較高和分佈較廣（如第4圖之高電阻侧 所示，即在圖上101°歐姆的地方）。Chi et al. further describe that negatively charged particles near the illumination zone may overcome the masking potential and adhere to the surface of the insulator. However, if the nano gold particles are directly adsorbed by this method, the electrostatic charge lines in this case are usually widened due to the disordered scattering of the generated secondary electrons, and therefore, the widths of the plurality of particle lines are generated. Reducing the dose of the electron beam can reduce the number of gold particles adsorbed by reducing the attractive force, but often falls below the critical value of the adsorbed gold particles, and cannot truly achieve the purpose of adsorbing only a single particle. Here, a small amount of biotin-modified DNA molecules are first attracted by a static charge generated by a low-dose, highly focused electron beam. The sulfur in the biotin is then used to adsorb the gold particles in the solution. According to the method of the invention 12 200909810, an oligonucleotide molecule can be used to solve the problem of attraction between the gold particles and the substrate because they are smaller and lighter than the gold particles. Figures 1(a) through 1(g) show graphical representations of a scanning electron microscope (SEM) image of a single-line pattern of gold nanoparticles prepared by this method. Here, the length of the straight single-line particle chain in the first (b), 1 (d) and 1 (g) graphs varies from tens of nanometers to several tens of micrometers. In the special 1(a) diagram, 4 sets of gold particle patterns of the "DM" letters produced by different electron beam doses are shown. These patterns suggest that the appropriate line dose of the electron beam is between 2. 5 and 4.0 nC/cm. In this case, further increasing the dose causes more particles to be attracted together, making the single line width thicker, and thus causing the single line width to be larger than the particle size. Figure 1(g) shows an enlarged image of a single-line gold particle chain in which the average distance between two adjacent particles is approximately equal to the size of the particles. Thus, testing with electron beams at various pulse intervals did not result in a corresponding change in particle spacing. Therefore, the spacing of the particles is mainly due to the weak repulsive force between the gold particles, rather than the distance distribution from the electrostatic charges, and the inventors have determined that such a conclusion is reasonable. From the upper right to the lower left, the four sets of "DNA" letters generated in Figure 1(a) are exposed online at 1. 0, 1.5, 2.5, and 4. 0 nC/cm electron beam doses. under. In the figures 1(b) to 1(g), a single-line exposure dose of 2.5 nC/cm was used to produce the pattern. However, for all patterns, the center-to-center distance between electron beam pulses is set to a specific value. 6纳米。 In a preferred embodiment, the specific value is 13. 6 nm. Figure 2 shows an illustration of a complete 2009 20091010 full bridge cycle for making such a conductive nanowire. As shown in Figure 2, the application of the bridging cycle is repeated in Figure 2 to fill the larger gaps between the particles to form a gold nanoparticle wire with interparticle tunneling (see also 3(b) to 3). (g) Figure). Figures 3(a) through 3(g) show graphical representations of a scanning electron microscope image of one of the Victorian particle arrays and the nanowires, wherein Figure 3(a) shows the single line before the bridging cycle is implemented. The structure of Figures 3(b) and 3(c) shows the structure of a single line after a bridging cycle, and the figures 3(d) to 3(f) show the structure of a single line after the secondary bridging cycle. Figure 3(g) shows the gold particle nanowires fixed between the electrodes to produce electrical measurements, and as shown in Figure 3(g), in order to create electronic components, gold particles are required. Connect closely to allow conduction of electrons. The inventors have also determined that the more cycles applied, the lower the resistance of the wires will be, wherein the wires have linear current-voltage (I-Vb) characteristics at room temperature, and their resistance values are distributed in approximately two groups. Figure 4 is a diagram showing the strip distribution of the resistance function at room temperature for the number of samples and their parent 10 0 ηιπ. That is, Figure 4 shows the strip distribution of the resistance measured by the secondary bridged loop assembled wires. Refer to Figure 4 to clearly show that the wire has low resistance (high penetration) or very high resistance (low penetration). The behavior of such divergence can be attributed to two bridging mechanisms, namely (1) if the particles are only bound by biotin, the distance is small and the wire resistance is low, and (2) if the particles are 20-base poly-A When a mixture of nucleotide (5'-(A)20-3') or (20A) and 7-base poly-T-nucleotide (5'-(T)7-3') or (7T) is linked, The distance between the particles becomes larger than 200909810, and the wire resistance is higher and the distribution is wider (as shown on the high resistance side of Figure 4, which is 101° ohms on the figure).
第5(a)圖所示為具有電阻1. 5K歐姆的連結奈米顆 粒導線之I-Vb特性的圖示。參考第5(a)圖，所有低電 阻的導線顯示之非常穩定之線性I-Vb的關係，其中線 性的區域延伸至約0.3 mA的電流對此一 1.5K歐姆的電 阻。在有效導線直徑為10 nm的情況下，相當於2. 6xl08 A/cm2的電流密度，比在奈米級CMOS技術内使用之多層 銅導線的值大了約數百倍，如Im等人在IEEE Trans.Fig. 5(a) is a graph showing the I-Vb characteristics of the bonded nanoparticle wires having a resistance of 1.5 K ohm. Referring to Figure 5(a), all of the low-resistance wires show a very stable linear I-Vb relationship, where the linear region extends to a current of about 0.3 mA for this 1.5K ohm resistor. In the case where the effective wire diameter is 10 nm, the current density equivalent to 2. 6x10 A/cm2 is about several hundred times larger than the value of the multilayer copper wire used in the nano-scale CMOS technology, such as Im et al. in IEEE Trans. .
Vol. 52，pg. 2710 (2005)文中内所述的電子元件。 根據本發明的方法，假設使用兩個電極之間約10 個串聯的跳躍基點，則單一連結（junction)的電阻大約 為150歐姆。然而，實際上，一般接點電阻（c〇ntact resistance)估計大約為150歐姆，因此這些連結的電 阻估計將比150歐姆小很多。此導線之線性的電流一電 壓特性，以及高的電流密度，將可提供作為極小尺度下 之連接導線用途。 第5(b)圖所示為在各種偏壓下，一條在室溫下電 阻約33M歐姆之導線，經過栅電壓調節的源極 的電流圖。第5(b)圖所示的圖是在6 κ的溫度下所： 得。平行四邊形的庫倫零電流區和庫倫振盪是單電 移的特徵。本發明者已經確定在室溫下高—的導線^ 類似於低電阻導線的I-Vb線性特性，但是在加、 電阻的導線於低偏壓區_顯示出t 15 200909810 抑制電4巧楚地顯示出其隨著柵電壓（Vg)的調制而呈 =㈣現象^此性質可以g 5(b)圖的立體圖中清楚 ^的Ϊ電流平行四邊形來做最好的描述。零電流平行 、广疋歸因於金顆粒對周遭所感受到的微小電容因 /成的電荷效應’也因此在卜Vb特性内的庫偷阻斷 、I Vg特性内的庫倫振盪更加證實金顆粒在此環境 下的角色。當溫度由300K降到5K時，不論電阻的高 低，大部份導線的電阻增加約5〜20%。 第5(c)圖為同一導線在基材溫度為5Κ(曲線的較 ，品）和85Κ(曲線的較高區）之_卜化特性的圖。必 湏主意第5(c)圖内所示的圖，當基材溫度由87Κ降到 7Κ時曲線被垂直往下移動錢提供更明確的比較。在 低偏壓m *於庫儉阻斷效應，雖料線的電阻隨基 材溫度㈣低增加數千倍，但是在高偏壓區内導線^ ，，也就是連接_充電聽的修，僅增加約15%。 恤度降低時，導線内電阻的微幅增加顯示隨著顆粒之間 的距離有稍微增加，而低電壓區域的電阻急遽的增加顯 示導電電子在奈米顆粒之間隙中以” _，， _ 傳導。 订 至於結合顆粒的穩定性，即使基材溫度在6 5fK(25(rC：)之間改變時’雖結構敍騎完整。以 掃描式電子顯微鏡射轉—段長時間如多達6個 ==的=發明者已經確定甚至用水或两_ 用力的冲洗，並不會移動或料基材上之任何金顆粒。 200909810 因此’很明顯的在金顆粒與基材之間以及顆粒之間有很 強的結合力。 在電子的領域之外’此種奈米顆粒鏈的結構在經 由表面電漿共振之具有選擇性頻率反應的奈米光子方 面，亦有應用的潛力，並且亦能用來建造奈米級的波 導、開關、感應器專等。在物理學内，電聚是起因於電 漿振盪之量子化的準粒子，這類似於光波和聲波之量子 化的光子和聲子。因此，電漿是自由電子在光學頻率下 的集體振盪。 以光來做表面電漿的激發，稱為平面的表面電漿 共振（SPR)或奈米尺寸之金屬結構的局部表面電漿共振 (LSPR)。此現象是在平面的金屬表面上（例金和銀）或是 在金屬奈米顆粒表面上，測量材料之吸附的許多標準工 具的基礎。在許多以顏色為基礎之生物感應器的應用和 不同之實驗室晶片感應器皆以此基礎現象為依據。 由於顆粒内導電電子之集體振盪的共振的激發， 已知金奈米顆粒在光波長下有大的散射截面。因此，由 於局部電場的強化和強的散射，單顆粒大小的金奈米顆 粒鏈或導線在引導電磁能量上有很大的潛力。一個單顆 粒大小之金奈米顆粒鏈或導線的能力能把光的式樣轉 變成非輕射之電聚的表面，且能在繞射的極限外引導光 這是一般傳統的波導或光子晶體所無法達成。然而，本 =明的方法提供一種可準確控制位置的設計方法來製 迨此種金顆粒鏈或導線。因此，功能性奈米光學元件的 17 200909810 製造變成可能。 第6圖顯示為一條42微米長金奈米顆粒導線之表 面電漿共振的影像，這是使用一台倒立式的光學顯微鏡 的照相系統所獲得的。在此，包括一台彩色CCD照像機 (Nikon 70D)。而顯微鏡是具有40x物鏡的〇iympus 1X71。在此，奈米顆粒樣品是以鎢絲光源沿著導線的軸 向約43°下照亮。由於導線内導電電子的集體共振，可 以使用光學顯微鏡觀察到此種約50 nm寬的金奈米導 線。此觀察顯示光的彈性散射具有相當高的效率。第 3(d)圖顯示相同之導線的掃描式電子顯微鏡影像。 本發明之方法的一個範例，使用兩種生物素修飾 的寡核甘酸，如 5μΜ 5，-biotin-(A)2〇-3，和 5μΜ 5， -biotin-(T)7-3 ’ (MDBio, Inc., Taiwan)(即 biotin-20A和biotin-7T)。將每一個生物素修飾的寡 核甘酸懸浮在具有特定pH值的1. 0 Μ KH2P〇4溶液中。 在較佳實施例内，pH值為4. 3。準此，如Herne等人在 Chem. Soc.，Vol. 119, pg. 8916 (1997)文中内所述， 緩衝濃度在硫醇-金的相互作用内具有一個重要的角 色。為了將生物素和DNA分子連結起來，附有（CH2)6-段的生物素能與DNA分子之5’ -端作結合。因此，可 達到一個生物素-DNA的結構，在此將它稱作生物素修 飾之DNA。生物素含有硫醇基，對金奈米顆粒具很強的 結合力。 根據 Grabar 等人在 Anal· Chem.，Vol. 67，pg. 200909810 文中内所插述的程序，本發 :用：‘猶的檸檬酸鹽還原以製備金顆1:: 用一個以400 nm厚之教惫扎e 方使 a曰 片作為基材。…、乳化Sl〇2層所覆蓋之w職石夕Vol. 52, pg. 2710 (2005) Electronic components as described herein. According to the method of the present invention, assuming a hop base point of about 10 in series between two electrodes, the resistance of a single junction is about 150 ohms. However, in practice, the general contact resistance (c〇ntact resistance) is estimated to be approximately 150 ohms, so the resistance of these connections is estimated to be much smaller than 150 ohms. The linear current-voltage characteristics of this wire, as well as the high current density, will be available as a connecting wire for very small scales. Figure 5(b) shows the current diagram of the source regulated by the gate voltage for a conductor with a resistance of approximately 33 M ohms at room temperature under various bias voltages. The graph shown in Figure 5(b) is at a temperature of 6 κ: The Coulomb zero current region and Coulomb oscillation of the parallelogram are characteristic of a single electrotransfer. The inventors have determined that the wire-high at room temperature is similar to the I-Vb linearity of the low-resistance wire, but the wire in the plus-resistance is shown in the low-bias region _ t 15 200909810 It shows that it exhibits a = (four) phenomenon with the modulation of the gate voltage (Vg). This property can be best described by the Ϊ current parallelogram in the perspective view of the g 5(b) diagram. The zero current is parallel and the 疋 is attributed to the charge effect of the tiny particles caused by the gold particles. Therefore, the coulomb oscillation in the Vb characteristic and the Coulomb oscillation in the I Vg characteristic confirm the gold particles. The role in this environment. When the temperature is lowered from 300K to 5K, the resistance of most of the wires increases by about 5 to 20% regardless of the high and low resistance. Fig. 5(c) is a graph showing the characteristics of the same wire at a substrate temperature of 5 Κ (ratio of the curve) and 85 Κ (the higher zone of the curve). The diagram shown in Figure 5(c) must provide a clearer comparison of the curve when the substrate temperature is lowered from 87Κ to 7Κ. In the low bias m * in the reservoir blocking effect, although the resistance of the wire increases thousands of times with the substrate temperature (four), but in the high bias region, the wire ^, that is, the connection _ charging listening repair, only Increase by about 15%. When the degree of the shirt is lowered, the slight increase in the resistance inside the wire shows a slight increase in the distance between the particles, and the rapid increase in the resistance in the low voltage region shows that the conductive electron is conducted in the gap of the nanoparticle by "_,, _ conduction As for the stability of the bonded particles, even if the substrate temperature is changed between 6 5fK (25 (rC:)', the structure is complete. The scanning electron microscope is used for a long period of time as long as 6 = = The inventor has determined that even with water or two rinsing, it does not move or feed any gold particles on the substrate. 200909810 Therefore 'very obvious between the gold particles and the substrate and between the particles Strong binding force. Outside the field of electronics, the structure of such nanoparticle chains has potential for application in the selective photoreaction of nanophotons via surface plasmon resonance, and can also be used for construction. Nano-scale waveguides, switches, inductors, etc. In physics, electropolymerization is a quasi-particle that results from the quantization of plasma oscillations, which is similar to the quantized photons and phonons of light waves and sound waves. Electricity It is the collective oscillation of free electrons at optical frequencies. The excitation of surface plasma by light is called surface surface plasma resonance (SPR) or local surface plasma resonance (LSPR) of metal structures of nanometer size. Phenomena are the basis of many standard tools for measuring the adsorption of materials on flat metal surfaces (eg gold and silver) or on the surface of metallic nanoparticles. The application and diversity of many color-based biosensors Laboratory wafer sensors are based on this fundamental phenomenon. Due to the excitation of the collective oscillation of the conductive electrons in the particles, it is known that the gold nanoparticles have a large scattering cross section at the wavelength of light. Therefore, due to the strengthening of the local electric field and Strong scattering, single-particle size gold nanoparticle chains or wires have great potential for guiding electromagnetic energy. The ability of a single particle-sized gold nanoparticle chain or wire can transform the pattern of light into a non-light shot. The surface of the electropolymer, and which can guide light outside the limits of diffraction, which is not possible with conventional conventional waveguides or photonic crystals. However, the method of the present invention provides a The design method of accurately controlling the position to make such a gold particle chain or wire. Therefore, the manufacture of functional nano-optical components 17 200909810 becomes possible. Figure 6 shows the surface plasma of a 42 micron long gold nanowire wire. The image of the resonance, which was obtained using a camera system with an inverted optical microscope. Here, a color CCD camera (Nikon 70D) was included. The microscope was a 〇iympus 1X71 with a 40x objective. The nanoparticle sample is illuminated with a tungsten light source at about 43° in the axial direction of the wire. Due to the collective resonance of the conductive electrons in the wire, such a 50 nm wide gold nanowire can be observed using an optical microscope. This observation shows that the elastic scattering of light has a relatively high efficiency. Figure 3(d) shows a scanning electron microscope image of the same wire. An example of a method of the invention, using two biotin-modified oligonucleotides, such as 5 μΜ 5,-biotin-(A)2〇-3, and 5 μΜ 5,-biotin-(T)7-3 ' (MDBio , Inc., Taiwan) (ie biotin-20A and biotin-7T). Each biotin-modified oligosaccharide was suspended in a 1.0 Μ KH2P〇4 solution having a specific pH. 5。 The preferred embodiment, the pH value of 4.3. As such, as described by Herne et al., Chem. Soc., Vol. 119, pg. 8916 (1997), the buffer concentration has an important role in the thiol-gold interaction. In order to link the biotin and the DNA molecule, the biotin attached to the (CH2) 6-stage can bind to the 5'-end of the DNA molecule. Therefore, a biotin-DNA structure can be achieved, which is referred to herein as a biotin-modified DNA. Biotin contains a thiol group and has a strong binding force to the gold nanoparticles. According to the procedure interspersed by Grabar et al., Anal Chem., Vol. 67, pg. 200909810, the present invention: using: citrate reduction to prepare gold particles 1: using a thickness of 400 nm The teachings are used to make a sheet as a substrate. ..., emulsified SlS2 layer covered w
根據本發明的方法，基材在被氮氣吹乾之前 在丙酮内清潔。然後在-個反應式的離子蝕刻器内作一 定時間的氧―電聚處理。在較佳實施例内，預定的： 是1分鐘。電漿處理有兩個目的。首先，它能 二 的有機化合物。第二，它能產㈣微帶有負電荷表= 防止DNA分子之非特定的結合。 下一步，將來自改裝之場發射的婦描式電子顯微 鏡（如FEI Sirion 200)的聚焦電子束，以電腦控 DAC(如由NPGS提供的DAC)引到特定的區域上，以便產 生嵌入靜電荷的式樣。在此，在調整電子束的程序時， 必須小心以避免任何不必要的電子束曝光，因為縱使極 微量的曝光也有可能造成不需要之靜電荷產生，以及隨 之而來的顆粒附著。 然後將生物素-20A的少量樣品放到基材樣品上 並維持一段長時間，以容許DNA分子的靜電吸引。隨 後’在將準備好的金顆粒溶液加到基材上的生物素_2〇a 之前’用去離子水洗淨基材樣品並吹乾。在較佳實施例 内，延長的時間是15分鐘。 在等待另一個預定的時間之後，容許金顆粒與生 物素内的硫原子之間產生結合，用去離子水再洗淨基材 19 200909810 樣品並吹乾，以供進一步的掃描式電子顯微鏡檢查。在 較佳實施例内，預定的時間是30分鐘。 根據本發明的一個實施例，使用一種橋接循環的 方法，將金顆粒緊密地結合在鏈内，如第2圖内所示的 方法。在此處，將生物素-7T溶液初步加入現有的金顆 粒鏈内以結合金顆粒和生物素。然後再加入金顆粒以便 在基材的表面上與生物素結合，或在金顆粒的表面上與 生物素結合。 下一步，將生物素-20A溶液加入單股的生物素-7T 中。在此，生物素-20A在金顆粒上與單股的生物素-7T 混成或直接結合至固定的金顆粒上。最後，加入額外的 金顆粒溶液以充填顆粒之間的間隙。注意在每一個步驟 之後，基材樣品需有洗滌和乾燥的程序。如此，可達 成一個將金顆粒***現有之金鏈内的橋接循環。 本發明的方法可供一種在指定之奈米位置上建造 單線顆粒鏈的方法。少量的正電荷被植入一個奈米級的 區域内，並使用一個具有適當應用劑量的電子束來吸引 一小叢的生物素修飾之DNA分子。然後這些生物素修 飾之DMA分子與金顆粒結合以形成所要的式樣。對於 電子上的應用，本發明的方法可使金顆粒建立可導電的 奈米導線。奈米電子和組合元件内使用之連接導線和單 電子電晶體的發展是本發明之方法的應用範例。並且， 需聲明本發明方法的實施例亦可應用於可被生物素修 飾的其它顆粒，如氧化鐵，碳-60(C60)或碳奈米顆粒。 20 200909810 此外’ f發明方法的實施例不只局限於上述討論的基 材仁疋對其匕基材亦同樣適用，包括所有絕緣的基材 或被塗上I絕緣層的導電基材。最後，本發明方法的 實施例亦可應用於上述討論之_分子以外的物質，例 如’它們可以被用於其它分子，如polypeptides或DNA 碎片。 以上所述僅為本發明之較佳 實施例而已，並非用 以限定本發明之申請專利範®;凡其它未脫離本發明所 揭示之精神下所完成之等效改變或修飾，均應包含在下 述之申睛專利範圍内。 【圖式簡單說明】 、第1(a)至Ug)圖所示為製造之金奈米顆粒之單線 式樣的掃描式電子顯微鏡(SEM)之影像的圖示； 第2圖所示為製造導電之奈米導線的一個完整橋 接循環步驟的圖示； 太、，第3(a)至3(g)圖所示為製造之一維金顆粒陣列和 不米導線的掃描式電子顯微鏡影像的圖示； 第4圖所示為樣品數與其每100奈米在室溫下電 阻函數的長條分佈圖的圖示； 第5(a)至5(c)圖所示為連結奈米顆粒導線之I-Vb 特性的圖示；以及 第6圖所示為一個根據本發明方法所示之42微米 長金不米顆粒導線的表面電漿共振影像的圖示。 21 200909810 【主要元件符號說明】 22According to the method of the present invention, the substrate is cleaned in acetone before being blown dry with nitrogen. The oxygen-electropolymerization treatment is then carried out for a certain period of time in a reactive ion etcher. In the preferred embodiment, the predetermined: is 1 minute. Plasma processing has two purposes. First, it can be an organic compound. Second, it produces (iv) micro-charged negative charge tables = preventing non-specific binding of DNA molecules. Next, focus the electron beam from a refractory electron microscope (such as FEI Sirion 200) from a modified field to a computer-controlled DAC (such as a DAC supplied by NPGS) to a specific area to generate an embedded electrostatic charge. The style. Here, care must be taken in the adjustment of the electron beam to avoid any unnecessary electron beam exposure, because even a very small amount of exposure may cause unwanted static charge generation and the accompanying adhesion of particles. A small sample of biotin-20A is then placed on the substrate sample and held for a long period of time to allow electrostatic attraction of the DNA molecules. Subsequently, the substrate sample was washed with deionized water and blown dry before adding the prepared gold particle solution to biotin 2〇a on the substrate. In the preferred embodiment, the extension time is 15 minutes. After waiting for another predetermined time, a bond is allowed between the gold particles and the sulfur atoms in the biotin, and the substrate 19 200909810 sample is washed again with deionized water and blown dry for further scanning electron microscopy. In the preferred embodiment, the predetermined time is 30 minutes. According to one embodiment of the invention, gold particles are tightly bonded within the chain using a bridging cycle method, as shown in Figure 2. Here, the biotin-7T solution was initially added to the existing gold particle chain to bind the gold particles and biotin. Gold particles are then added to bind to biotin on the surface of the substrate or to biotin on the surface of the gold particles. Next, the biotin-20A solution was added to a single strand of biotin-7T. Here, biotin-20A is mixed or directly bonded to the immobilized gold particles on the gold particles with a single strand of biotin-7T. Finally, an additional gold particle solution is added to fill the gap between the particles. Note that after each step, the substrate sample is subjected to a washing and drying procedure. In this way, it is possible to achieve a bridging cycle in which gold particles are inserted into the existing gold chain. The method of the present invention provides a method of constructing a single strand of particulate chains at a designated nanometer location. A small amount of positive charge is implanted in a nanoscale region and an electron beam with the appropriate applied dose is used to attract a small cluster of biotin-modified DNA molecules. These biotin-modified DMA molecules are then combined with gold particles to form the desired pattern. For electronic applications, the method of the present invention allows gold particles to form electrically conductive nanowires. The development of connecting wires and single-electron transistors used in nanoelectronics and composite components is an application example of the method of the present invention. Moreover, it is to be noted that embodiments of the method of the invention can also be applied to other particles that can be modified by biotin, such as iron oxide, carbon-60 (C60) or carbon nanoparticles. 20 200909810 Furthermore, embodiments of the invention are not limited to the substrates discussed above, but are equally applicable to their substrates, including all insulating substrates or conductive substrates coated with an I insulating layer. Finally, embodiments of the method of the invention may also be applied to substances other than the molecules discussed above, e.g., they may be used in other molecules, such as polypeptides or DNA fragments. The above is only the preferred embodiment of the present invention, and is not intended to limit the scope of the present invention. Any equivalent changes or modifications which are not departing from the spirit of the present invention should be included. Within the scope of the patent application. [Simple description of the drawings], Figures 1(a) to Ug) show an image of a single-line scanning electron microscope (SEM) image of the manufactured gold nanoparticles, and Figure 2 shows the production of conductive Illustration of a complete bridging cycle of the nanowires; too, Figures 3(a) through 3(g) show diagrams of a scanning electron microscope image of one of the Victorian particle arrays and the non-wires. Figure 4 is a graphical representation of the strip distribution of the number of samples and their resistance function per 100 nm at room temperature; Figures 5(a) through 5(c) show the bonding of nanoparticle wires A graphical representation of the I-Vb characteristics; and Figure 6 is a graphical representation of a surface plasma resonance image of a 42 micron long gold grained wire shown in accordance with the method of the present invention. 21 200909810 [Main component symbol description] 22